The Threat of the South African Coronavirus Variant

The euphoria from the beginning of vaccination against COVID-19 is disturbed by discovering several distinct virus variants that could escape the protection of the current vaccines. Here we discuss perhaps the most worrying variant of the time, first identified in South Africa. 

The South African coronavirus variant is named B.1.351 (sometimes referred to as 501Y.V2). The detection of this coronavirus variant was first announced on December 18, 2020, in South Africa¹. It has largely replaced the variant circulating in the area, which suggested increased transmissibility. Since then, it has been reported in more than 30 countries, including other regions of Africa and countries on different continents - Belgium, France, Germany, the USA, Australia, and even some in Asia².

Importantly, it has three mutations in the key region of the virus’s spike protein. Spike proteins are present on the coronavirus’s surface. It is the part of the virus used for immunization via vaccines, making mutations in that region particularly disturbing. One of them is the N501Y mutation in the receptor-binding domain (also present in the British variant B.1.1.7) and is the cause of the higher transmissibility of these coronavirus variants³. Two other important mutations of the spike protein present in the South African strain are K417N and E484K – the first contributes to the higher transmissibility of the variant, and the latter serves as an escape mutant against the immune system since it interferes with the ability of antibodies to bind to this region⁴. Altogether, the mutations make the strain much easier to spread and potentially more resistant to antibodies against the previous variants, making it quite dangerous. However, there is no clear evidence that it makes the COVID-19 disease more severe. 

Do the current vaccines work against this coronavirus variant? The ability of the available vaccines to neutralize the mutant virus variant is being tested. Preliminary results of Pfizer vaccine-elicited sera showed small effects of these mutations on virus neutralization, which is good news for all the people who had previously been vaccinated with the Pfizer vaccine. However, this study’s sample size was very small (20 participants), and the tested virus contained only some of the mutations present in the South African variant⁵. Data on the Moderna vaccine show a six-fold reduction in neutralizing titers observed with the B.1.351 variant compared to prior variants. However, the much-lower levels are still expected to be protective⁶. Moderna announced its strategy to test an additional booster dose of its mRNA-1273 vaccine to further increase the neutralizing titers against emerging strains. They are also preparing a specific booster candidate vaccine – mRNA-1273.351 against the B.1.351 variant⁶. 

The AstraZeneca vaccine’s efficacy against mild to moderate disease was only 21.9% in the South African trial. In light of these results, the plans to vaccinate the South African population with the available 1 million doses of the AstraZeneca vaccine were put on hold. The Oxford-AstraZeneca team has already begun to work on a second-generation vaccine that targets the South African coronavirus variant⁷. The famous “first registered” COVID-19 vaccine – Sputnik V – is also currently being tested against the South African variant⁸. 

Other vaccines that await their approval also test their efficacy against the South African coronavirus variant. The vaccine developed by Johnson & Johnson had 85% efficacy against COVID-19-related fatalities or severe symptoms. It was similarly effective against severe disease in South Africa, but its efficacy in preventing moderate to severe COVID-19 dropped to 57%⁹. Novavax announced an 89.3% efficacy of their NVX-CoV2373 vaccine in its clinical trial conducted in the UK; however, their South African trial achieved overall efficacy of only 49.4% (up to 60% in the HIV-negative population)¹⁰. 

Since the more transmissible coronavirus variants can dramatically dominate among the people infected with COVID-19, it is essential to test all the vaccines face-to-face with these variants. Overall, the available data suggest that the vaccines in circulation offer some protection against this coronavirus variant. Multiple vaccine manufacturers are already working on a specialized vaccine version against these variants. In the meantime, when most people are not yet vaccinated, it is social distancing, mask-wearing, and good hand hygiene that are vital in protecting ourselves against COVID-19. 

References

1. https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/
2. https://cov-lineages.org/global_report_B.1.351.html
3. Padilla-Sanchez V (2021) SARS-CoV-2 Structural Analysis of Receptor Binding Domain New Variants from United Kingdom and South Africa. Research Ideas and Outcomes 7: e62936. https://doi.org/10.3897/rio.7.e62936
4. J. Greaney et al., “Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies,” bioRxiv, p. 2020.12.31.425021, Jan. 2021.
5. Xie, X., Liu, Y., Liu, J. et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nat Med (2021). https://doi.org/10.1038/s41591-021-01270-4
6. https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against
7. https://www.sciencemag.org/news/2021/02/south-africa-suspends-use-astrazenecas-covid-19-vaccine-after-it-fails-clearly-stop
8. https://www.businessinsider.co.za/sputnik-is-testing-for-south-african-variant-2021-2
9. https://www.prnewswire.com/news-releases/johnson--johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial-301218035.html
10. https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3

Image by Gerd Altmann from Pixabay